The methylation status of the TMS1/ASC gene in cholangiocarcinoma and its clinical significance.

Background: TMS1/ASC is a bipartite protein comprising two protein-protein interactive domains: pyrin (PYD) and caspase recruitment domain (CARD). Proteins containing these domains play pivotal roles in regulating apoptosis and immune response pathways. The absence of TMS1/ASC expression in some tumors is because methylation of the TMS1/ASC gene contributes to carcinogenesis and cancer development. We studied the methylation status of the TMS1/ASC gene and its clinical significance in cholangiocarcinoma.

Methods: Target DNA was modified by sodium bisulfite, coverting all unmethylated, but not methylated, cytosines to uracil, and subsequently by a nested amplification with primers specific for methylated versus unmethylated DNA. The PCR product was detected by gel electrophoresis and combined with the clinical records of patients.

Results: Aberrant methylation of the TMS1/ASC gene was detected in specimens of colorectal cancer tissues from 13 (36.1%) of 36 patients, and specimens of adjacent normal tissues from 3 patients (8.3%). No statistical differences were seen in the extent of differentiation and invasion, lymph node metastasis, and pathologic type between the methylated and unmethylated tissues (P>0.05).

Conclusions: The frequency of TMS1/ASC gene methylation in cholangiocarcinoma is high, but it is not related to pathologic changes. The TMS1/ASC gene is probably suppressed by methylation, and is resistant to apoptosis and immunological surveillance. The gene epigenetically affected in methylated tissues could be associated with carcinogenesis of cholangiocarcinoma.